The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin.

BACKGROUND: Cross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. OBJECTIVE: We wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. METHODS: The Global Asthma and Allergy Network of Excellence (GA(2) LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. RESULTS: One thousand nine hundred and fifty-five subjects aged 16-77 years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P = 0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. CONCLUSIONS AND CLINICAL RELEVANCE: Asthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.

The association of asthma, atopy and lung function with hormone replacement therapy and surgical cessation of menstruation in a population-based sample of English women.

BACKGROUND: Gynaecological surgery that may lead to cessation of menstruation is a major indication for the use of hormone replacement therapy (HRT) which in turn has been associated with asthma. METHODS: Information on asthma-like symptoms, lung function and immunoglobulin E (IgE) sensitization to house dust mite (HDM) and on menstrual status and use of HRT was collected from 3724 women aged between 35 and 64 years living in England. Association of health outcomes with use of HRT and with surgery resulting in cessation of menstruation was examined in multivariable models. RESULTS: Over a third of women who had ever used HRT had undergone surgery resulting in cessation of menstruation. Current use of HRT was associated with frequent wheeze, particularly in lean women [body mass index (BMI) < 25; odds ratio (OR) 1.90; 95% confidence interval (CI) 1.17-3.05; BMI 25+; OR 1.02; 95% CI 0.69-1.51]. Wheeze was associated with the reporting of menstrual cessation that was due to surgery even if women denied ever using HRT (OR 1.55; 95% CI 1.09-2.20). There was some evidence that HRT use was associated with airway obstruction in leaner women but little evidence that it was associated with IgE sensitization to HDM. CONCLUSIONS: In this cross-sectional study use of HRT was associated with asthma-like symptoms, particularly in those who have lower BMI. A substantial proportion of women whose periods have stopped because of surgery use HRT but this does not fully explain their increased morbidity.

Eczema, atopy and allergen exposure in adults: a population-based study.

BACKGROUND: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. OBJECTIVE: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. METHODS: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. RESULTS: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. CONCLUSIONS: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.

Association of lung function decline with the heme oxygenase-1 gene promoter microsatellite polymorphism in a general population sample. Results from the European Community Respiratory Health Survey (ECRHS), France.

Inducible heme oxygenase (HO-1) acts against oxidants that are thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD), characterised by impaired lung function. A (GT)(n) repeat polymorphism in the HO-1 gene promoter can modulate the gene transcription in response to oxidative stress. We hypothesised that this polymorphism could be associated with the level of lung function and decline in subjects exposed to oxidative aggression (smokers). We genotyped 749 French subjects (20-44 years, 50% men, 40% never smokers) examined in both 1992 and 2000 as part of the ECRHS. Lung function was assessed by forced expiratory volume in 1 second (FEV1) and FEV1/forced ventilatory capacity (FVC) ratio. We compared long (L) allele carriers ((GT)(n) > or =33 repeats for one or two alleles) to non-carriers. Cross sectionally, in 2000, L allele carriers showed lower FEV1/FVC than non-carriers. During the 8 year period, the mean annual FEV1 and FEV1/FVC declines were -30.9 (31.1) ml/year and -1.8 (6.1) U/year, respectively. FEV1/FVC decline was steeper in L allele carriers than in non-carriers (-2.6 (5.5) v -1.5 (6.4), p = 0.07). There was a strong interaction between the L allele and smoking. In 2000, the L allele was associated with lower FEV(1) and FEV(1)/FVC in heavy smokers (> or =20 cigarettes/day) only (p for interaction = 0.07 and 0.002 respectively). Baseline heavy smokers carrying the L allele showed the steepest FEV1 decline (-62.0 (29.5 ml/year) and the steepest FEV1/FVC decline (-8.8 (5.4 U/year) (p for interaction = 0.009 and 0.0006). These results suggest that a long (L) HO-1 gene promoter in heavy smokers is associated with susceptibility to develop airway obstruction.

Incidence of asthma and net change in symptoms in relation to changes in obesity.

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.

Serum carotenoids, vitamins A and E, and 8 year lung function decline in a general population.

BACKGROUND: Oxidative stress is thought to have a major role in the pathogenesis of airway obstruction. A study was undertaken to determine whether subjects with low levels of antioxidants (serum beta-carotene, alpha-carotene, vitamins A and E) would be at a higher risk of accelerated decline in forced expiratory volume in 1 second (FEV1) as their lungs would be less protected against oxidative stress. METHODS: 1194 French subjects aged 20-44 years were examined in 1992 as part of the European Community Respiratory Health Survey (ECRHS); 864 were followed up in 2000 and 535 (50% men, 40% lifelong non-smokers) had complete data for analysis. RESULTS: During the 8 year study period the mean annual decrease in FEV1 (adjusted for sex, centre, baseline FEV1, age, smoking, body mass index and low density lipoprotein cholesterol) was 29.8 ml/year. The rate of decrease was lower for the subjects in tertile I of beta-carotene at baseline than for those in the two other tertiles (-36.5 v -27.6 ml/year; p = 0.004). An increase in beta-carotene between the two surveys was associated with a slower decline in FEV1. No association was observed between alpha-carotene, vitamin A, or vitamin E and FEV(1) decline. However, being a heavy smoker (> or =20 cigarettes/day) in combination with a low level of beta-carotene or vitamin E was associated with the steepest decline in FEV1 (-52.5 ml/year, p = 0.0002 and -50.1 ml/year, p = 0.010, respectively). CONCLUSIONS: These results strongly suggest that beta-carotene protects against the decline in FEV1 over an 8 year period in the general population, and that beta-carotene and vitamin E are protective in heavy smokers.

Changes in active and passive smoking in the European Community Respiratory Health Survey.

The aim of the present investigation was to study changes and determinants for changes in active and passive smoking. The present study included 9,053 adults from 14 countries that participated in the European Community Respiratory Health Survey II. The mean follow-up period was 8.8 yrs. Change in the prevalence of active and passive smoking was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. Determinants of change were analysed and the results expressed as adjusted hazard risk ratio (HRR) or odds ratio (OR). The prevalence of active smoking declined by 5.9% (5.1-6.8) and exposure to passive smoking in nonsmokers declined by 18.4% (16.8-20.0). Subjects with a lower educational level (HRR: 0.73 (0.54-0.98) and subjects living with a smoker (HRR: 0.45 (0.34-0.59)) or with workplace smoking (HRR: 0.69 (0.50-0.95)) were less likely to quit. Low socio-economic groups were more likely to become exposed (OR: 2.21 (1.61-3.03)) and less likely to cease being exposed to passive smoking (OR: 0.48 (0.37-0.61)). In conclusion, the quitting rate was lower and the risk of exposure to passive smoking higher among subjects with lower socio-economic status. Exposure to other peoples smoking decreased quitting rates and increased the risk of starting to smoke.

Fruit and vegetable intakes and asthma in the E3N study.

BACKGROUND: A study was undertaken to investigate whether dietary intake predicted the prevalence of adult asthma among French women participating in the E3N study. METHODS: Of 68 535 women who completed a food frequency questionnaire in 1993 which included 238 food items, 2145 (3.1%) reported having asthma. The distribution of food intake was divided into quartiles (Q(1)-Q(4)) and the prevalence of asthma was compared between the different quartiles (lowest as reference) using logistic regression models on cross sectional data. RESULTS: After adjusting for age, body mass index, menopausal status, smoking status, total caloric intake, physical activity, and use of dietary supplements, women who had a greater intake of tomatoes (OR(Q1-Q4) 0.85 95% CI 0.75 to 0.96, test for trend p = 0.02), carrots (OR(Q1-Q4) 0.81 95% CI 0.72 to 0.92, test for trend p = 0.0003), and leafy vegetables (OR(Q1-Q4) 0.82 95% CI 0.73 to 0.93, test for trend p = 0.0009) had a lower prevalence of asthma. Apples were marginally related to the prevalence of asthma. No other fruits or vegetables were significantly associated with asthma prevalence. CONCLUSIONS: These results suggest that the intake of some vegetables may decrease the prevalence of adult asthma.

Association of bronchial hyperresponsiveness and lung function with C-reactive protein (CRP): a population based study.

BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated. METHODS: As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV(1)), and BHR to methacholine (>/=20% decrease in FEV(1) to <4 mg methacholine) were measured in 259 adults aged 28-56 years free of cardiovascular disease or respiratory infection. RESULTS: Mean (SD) FEV(1) (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p<0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects. CONCLUSIONS: Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.

An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages.

BACKGROUND: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects "at risk" of developing the disease. METHODS: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18,000 young adults (20-44 years) were analysed. RESULTS: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II-III. Moderate to heavy smoking (> or =15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR)=4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR=4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR=1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR=1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p<0.001), with no difference between stage 0 and COPD. CONCLUSIONS: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.

Perennial rhinitis: An independent risk factor for asthma in nonatopic subjects: results from the European Community Respiratory Health Survey.

BACKGROUND: Although clinical and experimental studies suggest that upper respiratory tract dysfunction may affect the lower airways, rhinitis is usually not studied as a potential risk factor for asthma. This is because both diseases share key elements of pathogenesis and are usually considered as different manifestations of the same underlying "atopic" state. OBJECTIVE: We sought to assess whether asthma is associated with rhinitis in the absence of immunologic disorders in a population study. METHODS: Data from 34 centers participating in the European Community Respiratory Health Survey were analyzed. Random samples of 20- to 44-year-old subjects were invited to complete a detailed questionnaire and undergo total and specific IgE measurements, skin prick tests to 9 allergens, and bronchoprovocation challenges with methacholine. RESULTS: Subjects with perennial rhinitis (n = 1412) were more likely than control subjects (n = 5198) to have current asthma. After adjustment for sex, age, smoking habit, family history of asthma, geographic area, and season at the time of examination, asthma was strongly associated with rhinitis among atopic subjects (odds ratio [OR] = 8.1; 95% confidence interval [CI] = 5.4-12.1) but also among nonatopic subjects (OR = 11.6; 95% CI = 6.2-21.9). Moreover, the association remained very strong when the analysis was restricted to nonatopic subjects with IgE levels of 80 kIU/L or less (OR = 13.3; 95% CI = 6. 7-26.5). In nonasthmatic subjects bronchial hyperresponsiveness was also more frequent in subjects with rhinitis than in those without rhinitis (OR = 1.7; 95%CI = 1.2-2.6 in nonatopic subjects with IgE levels of

Is bronchial hyperresponsiveness more frequent in women than in men? A population-based study.

To test the hypothesis that a greater proportion of women than men react to methacholine challenge and investigate the possible reasons for any differences observed, we recruited 495 subjects 20 to 44 yr of age (50.9% male) in Paris and 304 subjects (51.3% male) in Montpellier (France), as part of the European Community Respiratory Health Survey. The proportion of responders (PD20 < or = 4 mg methacholine) was 33.7% in women and 11.9% in men (odds ratio = 3.8; 95% confidence interval = 2.4-6.0) in Paris and 43.2% in women and 29.5% in men (odds ratio = 1.8; 95% confidence interval = 1.1-2.9) in Montpellier. These differences could not be explained by asthma, respiratory symptoms, atopy, or lung function parameters. In stepwise logistic regressions including sex, asthma, and asthma-like symptoms, nasal allergies, atopy, baseline FEV1, FEV1%pred, FVC, and FEV1%FVC, the odds-ratios for the effect of female sex on PD20 < or = 4 mg methacholine were 5.2 (3.0-9.0) in Paris and 2.2 (1.2-3.8) in Montpellier. Reacting to low doses of methacholine (PD20 < or = 0.5 mg) was associated with asthma and atopy in both men and women. In contrast, reacting to doses between 0.5 and 4 mg was associated with asthma and atopy only in men and with heavy tobacco consumption only in women. We conclude that the excess of hyperresponsiveness in women is not due to their having smaller lung size or airway caliber than men and may be related to a greater susceptibility to smoking.